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1.
Orv Hetil ; 158(49): 1953-1959, 2017 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-29199437

RESUMO

INTRODUCTION: The currently licensed seasonal influenza vaccines contain split, subunit or whole virions, typically in amounts of 15 µg hemagglutinin per virus strain for adult and up to 60 µg in elderly patients. AIM: The present study reports safety data of the newly licensed, reduced dose vaccine with 6 µg of hemagglutinin per strain produced by Fluart (Hungary) after its first season on the market. The main objective of enhanced safety surveillance was to detect a potential increase in reactogenicity and allergic events that is intrinsic to the product in near real-time in the earliest vaccinated cohorts. METHOD: The study methods were based on the Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU by the European Medicines Agency. STATISTICS: We used the Fisher exact test with 95% confidence intervals. RESULTS: We studied 587 patients and detected a total 24 adverse events, all of which have already been known during the licensing studies of the present vaccine. The frequencies of the adverse events were not different from what had been seen with the previously licensed 15 µg vaccine. CONCLUSIONS: Based on the results, the authors conclude that the new, reduced dose vaccine FluArt is safe and tolerable. Orv Hetil. 2017; 158(49): 1953-1959.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Vacinas contra Influenza/administração & dosagem , Estudos de Coortes , Glicoproteínas de Hemaglutininação de Vírus da Influenza/efeitos adversos , Humanos , Hungria , Vacinas contra Influenza/efeitos adversos , Vigilância de Produtos Comercializados/estatística & dados numéricos
2.
Mol Biol Rep ; 40(8): 4721-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23653002

RESUMO

We studied the role of isocitrate lyase in the interaction between Mycobacterium bovis BCG and mice. ApoB100-only LDLR-/- (B6;129S-ApoBtm2SgyLdlrtm1Her/J) mice were inoculated with M. bovis BCG harbouring plasmids carrying the gene for isocitrate lyase. The presence of ~29 times more copies of this gene resulted in a higher bacterial yield in the spleens and lungs of the infected mice. The spleen was 3-4 times heavier, and in the spleen the bacteria survived over 10 days longer than did the bacteria with the control plasmid. Propionate was less toxic for bacteria carrying icl plasmids in vitro. This recombinant BCG can be a possible vaccine candidate.


Assuntos
Vacina BCG/imunologia , Isocitrato Liase/metabolismo , Mycobacterium bovis/imunologia , Tuberculose/prevenção & controle , Animais , Apolipoproteína B-100/metabolismo , Vacina BCG/genética , Western Blotting , Primers do DNA/genética , Eletroporação , Feminino , Isocitrato Liase/genética , Pulmão/microbiologia , Camundongos , Camundongos Knockout , Plasmídeos/genética , Propionatos , Receptores de LDL/genética , Baço/microbiologia , Tuberculose/microbiologia
3.
In Vivo ; 30(6): 813-817, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27815466

RESUMO

BACKGROUND: One of the most important resistance mechanisms in bacteria is the increased expression of multidrug efflux pumps. To combat efflux-related resistance, the development of new efflux pump inhibitors is essential. MATERIALS AND METHODS: Ten phosphorus ylides were compared based on their MDR-reverting activity in multidrug efflux pump system consisting of the subunits acridine-resistance proteins A and B (AcrA and AcrB) and the multidrug efflux pump outer membrane factor TolC (TolC) of Escherichia coli K-12 AG100 strain and its AcrAB-TolC-deleted strain. Efflux inhibition was assessed by real-time fluorimetry and the inhibition of quorum sensing (QS) was also investigated. The relative gene expression of efflux QS genes was determined by real-time reverse transcriptase quantitative polymerase chain reaction. RESULTS: The most potent derivative was Ph3P=C(COC2F5)CHO and its effect was more pronounced on the AcrAB-TolC-expressing E. coli strain, furthermore the most active compounds, Ph3P=C(COCF3)OMe, Ph3P=C(COC2F5)CHO and Ph3P=C(COCF3)COMe, reduced the expression of efflux pump and QS genes. CONCLUSION: Phosphorus ylides might be valuable EPI compounds to reverse efflux related MDR in bacteria.


Assuntos
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Proteínas de Escherichia coli/antagonistas & inibidores , Escherichia coli/efeitos dos fármacos , Hidrocarbonetos Fluorados/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas da Membrana Bacteriana Externa/antagonistas & inibidores , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fluorometria/métodos , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Hidrocarbonetos Fluorados/química , Lipoproteínas/antagonistas & inibidores , Lipoproteínas/genética , Lipoproteínas/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Percepção de Quorum/efeitos dos fármacos , Percepção de Quorum/genética
4.
In Vivo ; 28(6): 1071-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25398801

RESUMO

BACKGROUND/AIM: Bacterial resistance to antibiotics has become a serious problem in antibacterial chemotherapy and resistance of bacteria to chemically-unrelated anti-microbial agents can be associated with the over-expression of efflux pumps. The simultaneous therapy with efflux pump inhibitors (EPIs) could be a solution to improve the effectiveness of antibiotics. The response of an organism to an EPI often depends on how that molecule fits a particular site of a protein. Because enantiomers of a given compound rotate plane-polarized light in a solution by the same angle but in opposite directions, the rational drug design should take the chirality into account if there is a difference between the racemic compound and its enantiomers. MATERIALS AND METHODS: The main goal of the present study was to elucidate the role of chirality of N-hydroxyalkyl-2-aminophenothiazines as effective EPIs by an automated method that uses the general efflux pump substrate ethidium bromide (EB) for the assessment of AcrAB-TolC system of wild-type Escherichia coli K-12 AG100. It has been shown that the most active EPIs among the N-hydroxyalkyl-2-aminophenothiazines were the compounds rac-3i, (+)-3i, and (-)-3i by modulating the AcrAB-TolC efflux pump. CONCLUSION: Comparison of effects of enantiomeric pairs revealed that their activities were similar to that of racemic derivatives. Moreover, there was no significant difference between the racemic compounds and their enantiomers related to their antibacterial and efflux pump inhibiting effects.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Proteínas de Escherichia coli/antagonistas & inibidores , Fenotiazinas/química , Fenotiazinas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli K12/efeitos dos fármacos , Escherichia coli K12/metabolismo , Testes de Sensibilidade Microbiana
5.
Acta Microbiol Immunol Hung ; 61(2): 229-39, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24939689

RESUMO

Even in asymptomatic cases of Chlamydia trachomatis infection, the aim of the antibiotic strategy is eradication of the pathogen so as to avoid the severe late sequelae, such as pelvic inflammatory disease, ectopic pregnancy, and tubal infertility. Although first-line antimicrobial agents have been demonstrated to be predominantly successful in the treatment of C. trachomatis infection, treatment failures have been observed in some cases. Rich source of antimicrobial peptides was recently discovered in Medicago species, which act in plants as differentiation factors of the endosymbiotic bacterium partner. Several of these symbiotic plant peptides have proved to be potent killers of various bacteria in vitro. We show here that 7 of 11 peptides tested exhibited antimicrobial activity against C. trachomatis D, and that the killing activity of these peptides is most likely due to their interaction with specific bacterial targets.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Bactérias/metabolismo , Chaperonina 60/metabolismo , Chlamydia trachomatis/efeitos dos fármacos , Medicago truncatula/química , Proteínas de Plantas/farmacologia , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Proteínas de Bactérias/isolamento & purificação , Chaperonina 60/isolamento & purificação , Chlamydia trachomatis/crescimento & desenvolvimento , Chlamydia trachomatis/metabolismo , Células HeLa , Humanos , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Proteínas de Plantas/síntese química , Proteínas de Plantas/isolamento & purificação , Ligação Proteica
6.
Acta Microbiol Immunol Hung ; 58(2): 123-34, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21715282

RESUMO

Chlamydophila pneumoniae is an obligate intracellular human pathogen, which causes acute respiratory tract infections and can also cause chronic infections. C. pneumoniae possess type III secretion system (TTSS), which allows them to secrete effector molecules into the inclusion membrane and the host cell cytosol. Low calcium response protein E (LcrE) is a part of TTSS. The gene of LcrE in a 6His-tagged form was cloned from C. pneumoniae CWL029, expressed and purified from Escherichia coli using the HIS-select TALON CellThru Resin, this gene was also cloned into a eukaryotic expression vector (pΔRC). One group of BALB/c mice received an intramuscular pΔRC inoculation then the mice were immunized with purified LcrE protein; the second group of mice was immunized two times with the recombinant plasmid (pΔRCLcrE), and the third group was primed with pΔRCLcrE inoculation then boosted with LcrE protein. LcrE-specific antibody response was induced by DNA immunization with a shift towards Th1 isotype pattern compared to protein-immunization, this shifting pattern was observed in plasmid primed then protein-boosted animals. DNA immunization given as a priming and followed by a protein booster significantly reduced the number of viable bacteria in the lungs after challenge with C. pneumoniae. These results confirm that immunization with pΔRCLcrE can be an effective part of a vaccination schedule against C. pneumoniae.


Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Vacinas Bacterianas/imunologia , Chlamydophila pneumoniae/imunologia , Vacinação , Vacinas de DNA/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Feminino , Imunoglobulina G/sangue , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C
7.
Acta Microbiol Immunol Hung ; 58(1): 13-22, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21450551

RESUMO

Mycobacterium smegmatis is a species of rapidly growing saprophytes with a number of properties that make it an effective vaccine vector. Recombinant M. smegmatis expressing protective antigens of different pathogens and molecules modulating the immune responses offers some potential for reduction of the burden of tuberculosis, HIV and hepatitis B infections. This paper discusses the molecular methods used to generate recombinant M. smegmatis and the results obtained with some of these recombinants.


Assuntos
Mycobacterium smegmatis/genética , Mycobacterium smegmatis/imunologia , Transformação Bacteriana/genética , Transformação Bacteriana/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Animais , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Antígenos HIV/biossíntese , Antígenos HIV/genética , Antígenos HIV/imunologia , Humanos
8.
Acta Microbiol Immunol Hung ; 56(4): 389-97, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20038490

RESUMO

Chlamydophila pneumoniae possesses a type III secretion system (TTSS), which allows the bacteria to secrete effector molecules into the inclusion membrane and into the cytosol of the host cell. Low calcium response protein H (LcrH), as a part of the TTSS, is a chaperone protein expressed from the middle to late stages of the chlamydial developmental cycle. Gene of LcrH (CPn0811) in a 6His-tagged form was cloned from C. pneumoniae CWL029, expressed and purified from Escherichia coli using the HIS-select TALON CellThru Resin. The purity was checked with mass spectrometry. The samples were used for immunization of BALB/c mice. The inducible E. coli clone, which over-expresses the chlamydial LcrH, permits the study of the biological properties of this protein.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Chlamydophila pneumoniae/metabolismo , Animais , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Infecções por Chlamydophila/imunologia , Infecções por Chlamydophila/microbiologia , Chlamydophila pneumoniae/química , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/imunologia , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C
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